A5002502994- Ion Transport and Channel Regulation
- Pancreatic function and diabetes
- Ion channel regulation and function
- Nitric Oxide and Endothelin Effects
- Renal function and acid-base balance
- Biomedical Research and Pathophysiology
- Electrolyte and hormonal disorders
- Mitochondrial Function and Pathology
- Renal and related cancers
- Hormonal Regulation and Hypertension
- Endoplasmic Reticulum Stress and Disease
- Cancer, Hypoxia, and Metabolism
- Neonatal Respiratory Health Research
- Immune Cell Function and Interaction
- Sodium Intake and Health
- Magnesium in Health and Disease
- Neuroscience and Neuropharmacology Research
- Alcohol Consumption and Health Effects
- Protein Degradation and Inhibitors
- Renin-Angiotensin System Studies
- Cellular transport and secretion
- Heat shock proteins research
- Physiological and biochemical adaptations
- Parathyroid Disorders and Treatments
- Immune cells in cancer
Université Paris Cité
2009-2024
Inserm
2013-2024
Sorbonne Université
2014-2024
Centre National de la Recherche Scientifique
2011-2024
Centre de Recherche des Cordeliers
2012-2024
Université Sorbonne Nouvelle
2020-2021
GTx (United States)
2018
Canadian Nautical Research Society
2017
Délégation Paris 5
2009-2016
Sorbonne Paris Cité
2016
Tight regulation of calcium levels is required for many critical biological functions. The Ca2+-sensing receptor (CaSR) expressed by parathyroid cells controls blood concentration regulating hormone (PTH) secretion. However, CaSR also in other organs, such as the kidney, but importance extraparathyroid metabolism remains unknown. Here, we investigated role using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition selectively increased renal tubular absorption and independent...
Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting polyuria reminiscent of antenatal Bartter’s syndrome.
Activation of the Na+-K+-2Cl−-cotransporter (NKCC2) and Na+-Cl−-cotransporter (NCC) by vasopressin includes their phosphorylation at defined, conserved N-terminal threonine serine residues, but kinase pathways that mediate this action are not well understood. Two homologous Ste20-like kinases, SPS-related proline/alanine-rich (SPAK) oxidative stress responsive (OSR1), can phosphorylate cotransporters directly. In process, a full-length SPAK variant OSR1 interact with truncated variant, which...
Sodium and its associated anions are the major determinant of extracellular fluid volume, reabsorption Na+ by kidney plays a crucial role in long-term blood pressure control. The goal this study was to investigate extent which inhibitors transepithelial transport (TNa) along nephron alter urinary solute excretion TNa efficiency how those effects may vary different segments. To accomplish that goal, we used multinephron model developed companion (28). That represents detailed transcellular...
Chronic metabolic acidosis (CMA) is associated with an adaptive increase in the bicarbonate absorptive capacity of rat medullary thick ascending limb (MTAL). To specify whether NHE-3, apical MTAL Na/H exchanger, involved this adaptation, NHE-3 mRNA was quantified by a competitive RT-PCR using internal standard which differed from wild-type 80-bp deletion. CMA increased 0.025+/-0.003 to 0.042+/-0.009 amol/ng total RNA (P < 0.005). transport activity measured as initial proton flux rate...
Decreases in blood pH activate NHE3, the proximal tubular apical membrane Na/H antiporter. In cultured renal epithelial cells, activation of endothelin-B (ETB) receptor increases NHE3 activity. To examine role ETB response to acidosis vivo, present studies examined receptor–deficient mice, rescued from neonatal lethality by expression a dopamine β-hydroxylase promoter/ETB transgene (Tg/Tg:ETB–/– mice). tubule suspensions Tg/Tg:ETB+/– 10–8 M endothelin-1 (ET-1) increased activity, but this...
This study aims to understand the extent which modulation of Na + -K -2Cl − cotransporter NKCC2 differential splicing affects NaCl delivery macula densa. absorption by thick ascending limb and densa cells is mediated apical NKCC2. A recent has indicated that modulated dietary salt (Schieβl IM, Rosenauer A, Kattler V, Minuth WW, Oppermann M, Castrop H. Am J Physiol Renal 305: F1139–F1148, 2013). Given markedly different ion affinities its splice variants, believed impact reabsorption. To...
Inactivating mutations of kidney Na-K-2Cl cotransporter NKCC2 lead to antenatal Bartter syndrome (BS) type 1, a life-threatening salt-losing tubulopathy. We previously reported that this serious inherited renal disease is linked the endoplasmic reticulum-associated degradation (ERAD) pathway. The purpose work characterize further ERAD machinery NKCC2. Here, we report identification ancient ubiquitous protein 1 (AUP1) as novel interactor ER-resident form in cells. AUP1 also an ER lectin OS9,...
Mutations in the anion exchanger pendrin are responsible for Pendred syndrome, an autosomal recessive disease characterized by deafness and goitre. Pendrin is highly expressed kidney collecting ducts, where it acts as a chloride/bicarbonate thereby contributes to regulation of acid-base homoeostasis blood pressure. The present study aimed characterize intrinsic properties pendrin. Mouse was transfected HEK (human embryonic kidney) 293 OKP (opossum proximal tubule) cells its activity...
Mutations in the renal specific Na-K-2Cl co-transporter (NKCC2) lead to type I Bartter syndrome, a life-threatening kidney disease featuring arterial hypotension along with electrolyte abnormalities. We have previously shown that NKCC2 and its disease-causing mutants are subject regulation by endoplasmic reticulum-associated degradation (ERAD). The aim of present study was identify protein partners specifically involved ERAD NKCC2. To this end, we screened cDNA library through yeast...
Apical bumetanide-sensitive Na(+)-K(+)-2Cl(-) co-transporter, termed NKCC2, is the major salt transport pathway in kidney thick ascending limb. NKCC2 surface expression subject to regulation by intracellular protein trafficking. However, partners involved trafficking of remain unknown. Moreover, studies aimed at under-standing post-translational have been hampered difficulty express mammalian cells. Here we were able renal epithelial cells tagging its N-terminal domain. To gain insights into...
The renal-specific Na-K-2Cl co-transporter, NKCC2, plays a pivotal role in regulating body salt levels and blood pressure. NKCC2 mutations lead to type I Bartter syndrome, life-threatening kidney disease. Regulation of trafficking behavior serves as major mechanism controlling activity across the plasma membrane. However, identities protein partners involved cell surface targeting are largely unknown. To gain insight into these processes, we used yeast two-hybrid system screen cDNA library...
Mutations in the electrogenic Cl(-)/H(+) exchanger ClC-5 gene CLCN5 are frequently associated with Dent disease, an X-linked recessive disorder affecting proximal tubules. Here, we investigate consequences Xenopus laevis oocytes and HEK293 cells of nine previously reported, pathogenic, missense mutations ClC-5, most them which located regions forming subunit interface. Two mutants trafficked normally to cell surface early endosomes, displayed complex glycosylation at like wild-type but...
The sodium-independent anion exchanger pendrin is expressed in several tissues including the kidney cortical collecting duct (CCD), where it acts as a chloride/bicarbonate and has been shown to participate regulation of acid-base homeostasis blood pressure. renal sympathetic nervous system known play key role development salt-induced hypertension. This study aimed determine whether may partly mediate effects β adrenergic receptors (β-AR) on salt handling. We investigated activity by...
The thick ascending limb (TAL) of rat kidney absorbs bicarbonate secondary to proton secretion, but displays both basolateral and luminal Na+/H+ exchange (NHE) activity. Several NHE genes, including NHE-1, NHE-2, NHE-3, NHE-4, are expressed in the kidney. To identify isoforms medullary TAL (MTAL), we used reverse transcription-polymerase chain reaction (RT-PCR) detect mRNAs for microdissected MTAL. RT-PCR amplification from total RNA was performed between two specific primers each isoform....
Mutations in MAGED2 cause transient Bartter syndrome characterized by severe renal salt wasting fetuses and infants, which leads to massive polyhydramnios causing preterm labor, extreme prematurity perinatal death. Notably, this condition resolves spontaneously parallel with developmental increase oxygenation. interacts G-alpha-S (Gαs). Given the role of Gαs activating adenylyl cyclase at plasma membrane consequently generating cAMP promote reabsorption via protein kinase A (PKA), we...
Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from ER constitutes limiting step maturation and cell surface expression. Yet, molecular mechanisms involved this process remain obscure. Here, we report identification of chaperone stress 70 protein (STCH) stress-inducible heat shock (Hsp70), as two novel binding partners ER-resident form NKCC2. STCH knock-down increased total expression whereas...